DE19837434C2 - Automatic chemical analysis device - Google Patents

Description

The invention relates to a automatic chemical analyzer.

A chemical analysis device is known from US Pat. No. 4,451,433 that uses a pipetting system stem for metered introduction of reagents, which is a pump Selector valve and a nozzle contains. By operating the single selector valve who the outlet channels of certain reagent containers connected to the pump, the a predetermined amount of reagent in the sample in the previously positioned reaction onsgefäß introduced.

From JP 63-131066 A is an automatic analysis device with a piston pump known in which the path of movement of a holder for reagent containers with intersects the trajectory of a holding device of a reaction vessel. A Reagent is released by a rotary piston that is drawn into the side wall of the arranged reagent container is integrated. The piston is driven by a linkage shifted by means of a drive unit coupled before each cycle. To When the reagent is drawn in, the piston is turned by 180 ° by a gear wheel rotates and thereby closes the suction opening and an outlet opening ge opens. Disadvantages are excessive consumption of reagents that are necessary lengthy rinsing processes, the risk of mixing rinsing fluids  liquid with the reagents and also the possibility of formation and deposition of residues.

In an automatic analysis device known from US 5,173,741 long cylindrical reaction containers in a row close together in one Link conveyor individually arranged axially displaceable, in the lower the reaction vessels are transported hanging and in the upper run the reaction vessels with the opening facing down are emptied and rinsed the. A variety of test tubes are in a row above the movement the reaction vessel is arranged and on rails to the left or right moveable. Since the reaction of the reagent with the sample in the individual reacti ons containers during their transport in the upper strand of the link chain must, because of the reaction times to be observed, the transport speed the conveyor chain with the reaction containers only be small, which means the throughput stung this known analyzer significantly limited. This applies in particular rem when a sample is first analyzed with a first reagent and in a second subsequent stage, a further analysis with a second Reagent takes place. In this case the direction of movement would have to be for the second stage the reaction vessel can be reversed or there would be two separate analysis units required. Finally, cleaning or keeping clean also prepares of the different reaction vessels has significant problems since the different Types of reaction liquid or reagents when the individual Re flow out of the action container on the arched slide and if necessary can mix.

Diaphragm micropumps are also available for dispensing known from small amounts of liquid, the z. B. turned into inkjet printers be set. Such a micro diaphragm pump also includes a first pump body Electrodes electrically insulated from each other with a voltage source are connected. A second pump body has an inner membrane. There is a separate one in the cavity between the two pump bodies fluid. The membrane is used to suck up liquid through static elec tricity and deformed to release the liquid by its restoring force. To the The membrane has a relatively high rigidity for this purpose. In long-term operation there are undesirable reductions in delivery rates due to material fatigue the relatively expensive membrane.

The object of the invention is to provide a chemical analyzer with a simple Reagent dosing system to create a low adjustable consumption Reagents and rinsing liquid enables and without frequent disassembly and Flushing can be operated.

This object is achieved by an automatic chemical analysis device with the features specified in claim 1.

Appropriate refinements and developments of the analysis device are in the Subclaims specified.

In the following, exemplary embodiments of the invention are described using the schematic drawing explained in more detail. Show it:

Fig. 1a, 1b, a chemical analysis apparatus in front view and in plan view,

Fig. 2 is a partial sectional view of the essential modules of the analyzer of Fig. 1,

Fig. 3, the reagent delivery part of Fig. 2 in top view,

Fig. 4 is an axial section of a micropump in the reagent supplying part,

Figure 5 cut. One usable in the analyzer gear pump in Axial,

Fig. 6 is a view of a reagent supply portion, in another embodiment,

Fig. 7 shows a reagent container,

Fig. 8 to 10 versions of micropumps in axial section.

In the analysis device shown in FIGS. 1 to 4, a sample holder 22 with tubes 21 arranged in a circle for samples 20 with a rotary drive 23 is arranged on a base 12 . A pipetting device 31 is positioned laterally next to the sample holder 22 and has a nozzle 32 for sucking a sample 20 out of its tube 22 , a drive 33 for lifting and rotating the nozzle 33 and a pump, not shown, for sucking the sample into the nozzle 32 and dispense from the nozzle 32 . For this purpose, the sample holder 22 is rotated by a rotary drive mechanism 23 in order to position a tube 22 under the nozzle 32 of the pipetting device 31 .

The plurality of reaction vessels 41 are arranged in a holding device designed as a turntable 42 . Each reaction vessel 41 dips with its lower part into a chamber 43 which is kept at a constant temperature by the flow of water. The reaction vessels 41 are successively moved by a drive 44 below the lowering position of the nozzle 32 . Above the turntable 42 two identically constructed reagent units 51 and 61 and a rinsing device 71 are also arranged. Furthermore, a spectral measuring element 81 is provided directly next to the turntable 42 .

The reagents unit 51 shown in Figs. 2, 3 in each comprises a plurality of reagent containers 52 in a reagent holder 53, micro pump 54 and a rotary drive 55 for the holder 53. In the reagent holder 53 , the reagent containers 52 are arranged in the circumferential direction around a central rod 56 . The number of membrane micropumps 54 corresponds to the number of reagent containers 52 . The micropumps 54 are arranged in the lower part of the reagent holder 53 . Each reagent container 52 has a bottom opening 521 for connection to a suction opening 541 of the associated micropump 54 when the reagent container 52 is pressed firmly against the lower part of the reagent holder 53 .

Each micropump 54 has a vertical outlet 542 for dispensing the reagent. The reagent containers 52 carry a magnetic coding 522 on one side surface, the data of which indicate the type of reagent. A magnetic code reader 531 is positioned on the reagent holder 53 in a suitable position. Instead of the magnetic coding, other suitable detection means, e.g. B. bar codes can be used. From the code reader 531 , signal lines lead to a processing unit 57 which is connected to a micropump control unit 58 . The reagent holder 53 is rotated by a rotary drive 55 .

The suction opening of each micropump 54 can be provided with a lid for opening and closing the connection opening in order to prevent a reagent container from being connected to the suction opening of the micropump 54 if its coding data do not match the coding of the reagent currently required, which is shown in FIG should be contained in the reagent container 52 .

With this arrangement, the reagent holder 53 and the micropump 54 do not have to be rinsed each time the reagent container 52 is replaced with another one.

The micropump 54 shown in Fig. 4 has an inlet valve, a pump chamber 547 , a diaphragm 546 , a vibrating plate 545 and an outlet valve 544 , which are arranged in this order from the inlet opening to the outlet opening. The vibrating plate 545 is connected to the micro pump control part 58 by drive signal lines shown. An alternating current signal characterizing the amount of reagent to be dispensed is applied to the opposite surfaces of the vibrating plate 545 by the micropump control part 58 , which vibrates the vibrating plate 545 with a frequency corresponding to the amount of reagent to be dispensed, which are transmitted to the membrane 546 .

The operation of the micropump described is as follows.

A predetermined amount of the sample 20 is drawn from one of the test tubes 21 into the nozzle 32 of the pipetting device 31 and introduced into a reaction vessel 41 positioned by the drive mechanism 33 . Thereupon this reaction vessel 41 is moved to the reagent introduction by rotating the turntable 42 by means of its drive 44 into the predetermined transfer position.

In the first reagent unit 51 , the reagent holder 53 is rotated until the outlet opening 542 of a specific micropump 54 for this sample is located exactly above the reaction vessel 41 . As soon as the reaction vessel 41 and the outlet opening 542 are aligned with one another, the predetermined amount of reagents is introduced into the reaction vessel 41 from the micro pump 54 controlled by the control part 58 . If a second reagent is to be added, the reaction vessel 41 is moved to the outlet opening of the second reagent unit 61 , and the above process is repeated.

If a third and fourth reagent is to be added, the respective reagent holder is rotated further, and these reagents are introduced into the reaction vessel 41 from the reagent containers thus positioned. After the supply of these reagents, reactions of the reagents with the sample begin, and the result is a coloring of the sample corresponding to the density of a component. Since the extent of the coloring corresponds to the density of the component, an absorption spectrum of a sample in the reaction container is detected by the spectroscopic measuring element 81 and the density of the component is determined in terms of quantity. After the measurement, the sample is sucked out of the reaction container 41 in the rinsing mechanism 71 and the inner wall of the reaction vessel is rinsed.

The micropump 54 shown in FIG. 4 is operated as follows: First, an AC signal is applied to both surfaces of the vibrating plate 545 by the micropump control part, the signal duration corresponding to the frequency with which the vibrating plate 545 should be vibrated. Accordingly, the vibrating plate 545 deforms to set the membrane 546 in vibration. When the membrane deforms downward, the inlet valve 543 is opened to draw the reagent 523 into the pump chamber 547 , and when the membrane then swings up, the outlet valve 544 is opened to discharge the reagent 523 from the pump chamber 547 . The amount of reagent released into the reaction vessel is proportional to the frequency of oscillation of the oscillating plate 545 and is set by the frequency of the excitation signal from the control part 58 .

The internal volume of the micropump 54 can be set to less than 100 µl if the thin membrane is used which has been produced by a suitable processing method. Accordingly, the amount of reagent that remains useless in the micropump can be reduced to less than 100 µl after switching off the device. Since the micropumps 54 are arranged in the lower part of the reagent holder 53 , the respective reagent can simply run down without a separate printhead, so that the micropump has a simple structure.

The gear micropump according to Fig. 5 comprises two toothed wheels 548 in a pump chamber 547, which are rotated in the arrow direction, and a reagent 523 sucks in through the inlet opening. The reagent passes through holding chambers 549 between the gears 548 and the wall of the pump chamber 547 , and is discharged from the outlet opening. The reagents 523 in the two holding chambers 549 are mixed together at the outlet opening before being dispensed. The gear wheels 546 are rotated by a motor 581 , which is controlled by a motor control part 582 .

In this embodiment, the amount of reagent can be adjusted by adjusting the angle of rotation the gears are changed. Because the reagent is released in the direction of gravity ben, no separate printing is required, so that a small and simple Pump can be used. As a result of the small pump, only the smallest remain Amounts of reagent in the pump chamber so that the unused residual amounts after stopping the device are minimal.

In this exemplary embodiment, too, one micropump 54 is provided exclusively for one reagent in order to prevent interactions between reagents. When the reagent containers 52 are inserted into the reagent holders 53 , data indicating the type of reagent in the reagent container 52 is detected by the code reader 532 . In processing element 58 , this data is compared with data from the assigned micropump. If these data match, the micropump is activated. However, if the data do not match, an alarm is triggered and a signal is transmitted to the micropump control part 58 to prevent the pumps from being driven. This reliably prevents the mixing of different reagents.

In the embodiment of FIG. 7, an incorrect connection between a reagent container 52 and the predetermined micropump 54 is reliably prevented. A pin 524 is provided near an outlet port 521 on the bottom of the reagent container 52 in a certain position. A blind hole 543 is formed next to the suction opening 5 in the reagent holder 53 in a certain position, the positions of the pin 524 and the blind hole 543 being coordinated with one another. Accordingly, only one reagent container suitable for a specific micropump can be connected and two different reagents are prevented from flowing through one and the same micropump.

To clean the micropumps 54 , rinsing liquid can be introduced into the respective micropump after removal of the reagent container. Since the individual micropumps are used exclusively for the same reagents, it is not necessary to rinse after each analysis process, which saves rinsing liquid, time and maintenance.

In the embodiment according to FIG. 6, a micropump 54 is arranged directly on the bottom of each reagent container 52 . When the reagent container is inserted into the reagent holder 53 52 is a circuit on the outer wall of the Reagenzi enbehälters 52 provided signal terminal 523 in contact with a signal to put 532, which is provided on the inner wall of the reagent holder 53 so that a drive signal for the respective micropump can be transferred. The signal connection 532 is connected to the control element 58 . Furthermore, a coding is attached to part of the signal connection 523 , which characterizes a certain reagent, the data being input into the processing unit 57 when the signal connection contacts the signal connection 532 . The reagent holder 53 has relatively large cutouts 533 in its base in order to prevent the reagent stream emitted by the pump from being obstructed. The reagent data read from the signal connection 532 is compared in the processing unit 57 with data stored there. The micropump 54 attached to the reagent container 52 starts on an operating signal from the control part 58 and conveys the reagent directly from the reagent container 52 into the reaction vessel 41 .

Since in this version the reagent no other component, such as. B. the reagent holder contacted, any contamination is excluded. The reagent in the reagent container can be completely consumed except for the remaining amount in the micropump 58 .

As mentioned above, the reagent holder 53 with the reagent containers 52 is driven by the rotary drive 55 arranged in the base. A drive mechanism may be provided in the upper part of the device, and may drive the suspended reagent holder. The reagent container can not only perform rotational movements, but also translational movements. In a similar way, the reaction vessels can also be moved on straight lines, it also being possible to bring different reaction vessels to the reagent filling point in succession.

In addition to two reagent units, only one or other units may also be provided.  

In the micropump 54 shown in FIG. 8, the pump chamber 547 is formed by a cover part 201 and an intermediate part 205 , and the inlet to the pump chamber 547 consists of an inlet opening 202 and an inlet channel 203 embodied in the cover part 201 . An inlet valve 543 is formed on the intermediate part 205 and serves as a resistance element. An outlet opening contains an outlet channel 20 formed in the cover part 201 and an outlet valve 544 formed on the intermediate part 205 , which serves as a resistance element.

The membrane 546 is driven by an assembly consisting of a stationary electrode 211 , a movable electrode 212 , a pressure pin 213 , an annular groove 215 and an outlet nozzle 214 arranged in the intermediate part 205 . The cover part 210 , the intermediate part 205 , a stationary electrode support plate 210 , the movable electrode 212 and the pressure pin 231 are joined together and form an integrated body.

The stationary electrode 211 and the movable electrode 212 are electrically insulated from one another by an insulating membrane. These components can e.g. B. by diffusion joining using an intermediate thin metal foil, by a surface-active joining technique, by joining using low-melting glass with an intermediate lead glass pane, by an anode joining technique with an intermediate Pyrex glass pane and by a Si joining technique using silicon plates with or can be joined together without silicon oxide films. Similar joining techniques can also be used.

When a voltage is applied to the mutually insulated electrodes 211 and 212 , the generated electrostatic force pulls the movable electrode 212 towards the stationary electrode 211 , whereby the pressure pin 213 on the movable electrode 212 pushes the membrane 546 in one direction, in which decreases the volume of the pump chamber 547 . Due to the increased internal pressure in the pump chamber 547 , the outlet valve 544 in the outlet channel 20 is opened and liquid is discharged from the outlet nozzle 214 .

When the voltage between the electrodes 211 and 212 is interrupted, the membrane 546 moves in the opposite direction due to its restoring forces, whereby the volume of the pump chamber 547 increases. The internal pressure in the pump chamber 547 drops. Valve 544 closes outlet channel 214 and inlet valve 543 opens inlet channel 203 . Thus, liquid flows into the pump chamber 547 through the inlet opening 202 . By repeating these processes, liquid can be pumped continuously.

The property of the inlet valve 543 corresponds essentially to that of the outlet valve 544 , since both valve members are formed as part of the intermediate part 205 , which simplifies the manufacture accordingly.

The disadvantages of conventional electrostatic micro diaphragm pumps, in particular the low discharge pressure, are avoided and reagent liquid can also be introduced into reaction vessels in which there is a certain gas pressure. By providing the annular groove 215 , the responsiveness of the membrane 546 can be improved, since the induced resistance between the most stationary electrode 211 and the membrane 546 is reduced. The amount of liquid conveyed by the membrane 546 in each process can be very small, so that the desired delivery rate can be precisely controlled at a high oscillation frequency of the membrane.

The micropump according to FIG. 9 differs from the embodiment according to FIG. 8 in that the membrane 546 is formed in the opposite direction, whereby the pump chamber 12 is reduced in size. A central projection on the membrane 546 is acted upon by the pressure pin 213 .

Liquid is conveyed when a voltage is applied to the fixed electrode 211 and the movable electrode 212 and thus an electrostatic force is induced, which pulls the movable electrode 212 to the fixed electrode 211 . Accordingly, the pressure pin 213 of the movable electrode 212 presses against the membrane 546 in the direction of a reduction in volume of the pump chamber 547 . The internal pressure in the pump chamber 547 rises and the outlet valve 544 in the outlet channel 204 opens, so that liquid flows out of the dispensing nozzle 214 . When the voltage between the stationary electrode 211 and the movable electrode 212 is interrupted, the membrane 546 is moved in the opposite direction by its restoring force, whereby the volume of the pump chamber 547 increases. Due to the reduced internal pressure in the pump chamber 547, the outlet valve 544 closes the outlet channel 204 and opens the inlet valve 543 in the inlet channel. Thus, liquid flows into the pump chamber 547 through the inlet opening 202 . Repetition of these processes means that liquid is continuously pumped. In this embodiment, too, a sufficiently high delivery pressure is achieved in order to convey liquid reagents into reaction vessels under gas pressure.

With a very small volume of the pump chamber, the resistance between the cover part 201 and the membrane 546 is relatively large. To reduce the resistance, a wider recess is formed in the cover part 201 , which faces the membrane 546 . To draw liquid into the micropump, the membrane 546 can be operated moderately at a drive frequency of less than 1 Hz.

The micropump according to Fig. 10 differs from the embodiment according to Fig. 9 in that the resistance of the intake valve 543 is lower than that of the outlet valve, while the characteristics of the intake valve and the exhaust valve in the embodiment of Fig. 9 are the same. Furthermore, a lower plate 216 is provided on the outside of the movable electrode 212 to protect the electrode and improve the shut-off of the liquid in the drain part.

The effects of the different valve resistances are as follows: If liquid is to be introduced into the micropump still filled with a gas, the inlet valve cannot be opened by a membrane deflection in the pump chamber if the resistances of the inlet opening and the outlet opening are equal. This means that no liquid can flow into the pump chamber. For this reason, the resistance of the inlet valve 543 is reduced to a very small value and the freely projecting valve member of the insert valve 543 cannot come into close contact with the inlet opening 202 to maintain a gap therebetween, through which the liquid into the micropump of one Level above the inlet opening 202 can only flow in under the effect of the potential energy.

When the micropump starts, the outlet valve remains with greater resistance closed until the liquid is filled into the micropump and the gas from the Micropump flowed out through the inlet opening and in the pump chamber of the liquid has been displaced. Furthermore, the membrane of the Mi kropump during the introduction process with a relatively low frequency of less than 1 Hz can be operated.

Claims (11)

1. Automatic chemical analysis device with

• a sample holder ( 22 ) with test tubes ( 21 ),
• - A rotatable reagent holder ( 53 ) for holding a plurality of reagent containers ( 52 ),
• - A rotatable reaction vessel ( 42 ) for holding a plurality of reaction vessels ( 41 ) and
• a micropump ( 54 ) under the bottom part of each reagent container ( 52 ),

wherein the reagent holder ( 53 ) is arranged above the reaction vessel holder ( 42 ), the circular transport path of the reagent containers ( 52 ) and the circular transport path of the reaction vessels ( 41 ) overlap, and a reagent from the respective reagent container ( 52 ) is transferred into a reaction vessel ( 41 ) by means of the respective micropump ( 54 ). 2. Analysis device according to claim 1, characterized in that the micro pumps ( 54 ) are installed in the lower part of the reagent holder ( 53 ). 3. Analysis device according to claim 1, characterized in that on the Bo each reagent container ( 52 ) has a micropump ( 54 ) attached. 4. Analysis device according to one of claims 1 to 3, characterized in that the reaction vessel holder ( 42 ) is designed as a turntable, in the peripheral edge of which the reaction vessels ( 41 ) are arranged. 5. Analysis device according to one of claims 1 to 4, characterized in that the micropumps ( 54 ) are gear pumps or diaphragm pumps. 6. Analysis device according to claim 5, characterized in that each membrane pump ( 54 ) on one side of its membrane ( 546 ) has a stationary electrode ( 211 ) and an electrically insulated movable electrode ( 212 ) with a pressure pin ( 213 ), which Transmits electrode movements on the membrane ( 546 ). 7. Analysis device according to one of claims 1 to 6, characterized in that between the outlet opening ( 521 ) each in the reagent holder ( 53 ) a settable reagent container ( 52 ) and the suction opening ( 541 ) of the respectively assigned micropump ( 54 ) sealing means are. 8. Analysis device according to one of claims 1 to 7, characterized in that each reagent container ( 52 ) is marked with a code identifying the type of reagents ( 522 ), that the reagent holder ( 53 ) reading means ( 532 ) for detecting and storing the are assigned to respective codes and that a control mechanism ( 58 ) is present which activates the respective micropump ( 54 ) in accordance with the read code data. 9. Analysis device according to one of claims 1 to 8, characterized in that on the reagent holder ( 53 ) and on the positionable therein reagent containers ( 52 ) matching indexing elements ( 521 , 543 ) are arranged. 10. Analysis device according to one of claims 1 to 9, characterized in that the internal volume of each micropump ( 54 ) from its suction opening ( 202 ) to the outlet opening ( 214 ) is less than 200 µl. 11. Analysis device according to one of claims 5 to 10, characterized in that the resistances of the inlet valves ( 543 ) of the diaphragm pumps ( 54 ) are smaller than the resistances of the associated outlet valves ( 544 ).